1-12824959-C-A

Position:

• chr1-12824959-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001146344.3(PRAMEF11):​c.1420G>T​(p.Asp474Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PRAMEF11 NM_001146344.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.728

Genes affected

PRAMEF11 (HGNC:14086): (PRAME family member 11) Predicted to be involved in several processes, including negative regulation of apoptotic process; negative regulation of transcription, DNA-templated; and positive regulation of cell population proliferation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11034417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRAMEF11	NM_001146344.3	c.1420G>T	p.Asp474Tyr	missense_variant	4/4	ENST00000619922.1	NP_001139816.2
PRAMEF11	XM_011541479.3	c.1420G>T	p.Asp474Tyr	missense_variant	3/3		XP_011539781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRAMEF11	ENST00000619922.1	c.1420G>T	p.Asp474Tyr	missense_variant	4/4	1	NM_001146344.3	ENSP00000480027.2

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458474 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725446

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2024

The c.1294G>T (p.D432Y) alteration is located in exon 4 (coding exon 3) of the PRAMEF11 gene. This alteration results from a G to T substitution at nucleotide position 1294, causing the aspartic acid (D) at amino acid position 432 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	0.082
DANN	Benign	0.90
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.00086	N
M_CAP	Benign	0.00054	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.87	T
PrimateAI	Benign	0.37	T
Sift4G	Benign	0.13	T
Vest4		0.13
MVP		0.055
ClinPred		0.33	T
GERP RS		0.36
Varity_R		0.039
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-12884817; COSMIC: COSV70819989; COSMIC: COSV70819989;